## NULL
| Characteristic | M samples | Final analysis group, M samples = 15051 | Not in final analysis group, M samples = 1871 |
|---|---|---|---|
| Prenatal maternal smoking | 1,692 | ||
| Not exposed | 1,205 (80%) | 142 (76%) | |
| Smoke exposed | 300 (20%) | 45 (24%) | |
| Age at DNA methylation sample | 1,692 | ||
| Age 15 | 749 (50%) | 110 (59%) | |
| Age 9 | 756 (50%) | 77 (41%) | |
| Polymethylation score: coefficients for sustained smoking from newborn cordblood meta-analysis, w/ cell-type control (mean-centered) | 1,692 | 0.00 (0.23) | -0.01 (0.24) |
| AHHR: cg05575921 | 1,692 | 77.1 (5.8) | 75.3 (7.5) |
| Pediatric clock | 1,692 | 10.31 (1.93) | 10.51 (1.85) |
| Global methylation | 1,692 | 47.51 (0.80) | 47.42 (0.90) |
| Immune cell proportion (saliva) | 1,692 | 0.94 (0.13) | 0.93 (0.15) |
| Epithelial cell proportion (saliva) | 1,692 | 0.06 (0.13) | 0.07 (0.15) |
| Ancestry categorization from child principal components of genetic data | 1,669 | ||
| African ancestry | 907 (60%) | 78 (48%) | |
| European ancestry | 236 (16%) | 19 (12%) | |
| Hispanic ancestry | 362 (24%) | 67 (41%) | |
| Unknown | 0 | 23 | |
| Child gender | 1,692 | ||
| Boy | 741 (49%) | 107 (57%) | |
| Girl | 764 (51%) | 80 (43%) | |
| Maternal prenatal alcohol use | 1,688 | 173 (11%) | 20 (11%) |
| Unknown | 0 | 4 | |
| Maternal prenatal any drug use | 1,686 | 73 (4.9%) | 11 (6.1%) |
| Unknown | 0 | 6 | |
| Constructed - Poverty ratio - mother's household income/poverty threshold | 1,692 | 2.22 (2.43) | 2.35 (2.55) |
| Any postnatal maternal smoking when child age 1 or 5 | 1,604 | ||
| Maternal smoking at age 1 or age 5 | 592 (39%) | 52 (53%) | |
| No maternal smoking at age 1 and 5 | 913 (61%) | 47 (47%) | |
| Unknown | 0 | 88 | |
| Maternal/primary care giver smoking in month prior to visit (pks/day) | 1,674 | ||
| Less than pack a day | 338 (22%) | 43 (25%) | |
| No smoking | 1,059 (70%) | 115 (68%) | |
| Pack or more a day | 108 (7.2%) | 11 (6.5%) | |
| Unknown | 0 | 18 | |
|
1
n (%); Mean (SD)
|
|||
## png
## 2
| Characteristic | Age 9 | Age 15 | ||||||
|---|---|---|---|---|---|---|---|---|
| N | Not exposed, N = 6001 | Smoke exposed, N = 1561 | p-value2 | N | Not exposed, N = 6051 | Smoke exposed, N = 1441 | p-value2 | |
| Child characteristics | ||||||||
| Polymethylation score for smoke exposure | 756 | -0.04 (0.22) | 0.09 (0.23) | <0.001 | 749 | -0.01 (0.22) | 0.11 (0.23) | <0.001 |
| AHRR gene: percent cg05575921 methylation | 756 | 77.8 (5.2) | 76.8 (5.6) | 0.039 | 749 | 77 (6) | 76 (6) | 0.2 |
| Pediatric epigenetic clock (years) | 756 | 9.00 (0.85) | 9.01 (1.22) | 0.9 | 749 | 11.63 (1.77) | 11.64 (1.80) | >0.9 |
| Percent global DNA methylation | 756 | 47.51 (0.74) | 47.59 (0.78) | 0.2 | 749 | 47.48 (0.85) | 47.58 (0.83) | 0.2 |
| Immune cell proportion (saliva) | 756 | 0.96 (0.10) | 0.96 (0.08) | 0.3 | 749 | 0.92 (0.15) | 0.93 (0.14) | >0.9 |
| Epithelial cell proportion (saliva) | 756 | 0.04 (0.10) | 0.04 (0.08) | 0.3 | 749 | 0.08 (0.15) | 0.07 (0.14) | >0.9 |
| Ancestry categorization from child principal components of genetic data | 756 | <0.001 | 749 | 0.002 | ||||
| African ancestry | 356 (59%) | 98 (63%) | 364 (60%) | 89 (62%) | ||||
| European ancestry | 82 (14%) | 35 (22%) | 85 (14%) | 34 (24%) | ||||
| Hispanic ancestry | 162 (27%) | 23 (15%) | 156 (26%) | 21 (15%) | ||||
| Child gender | 756 | 0.7 | 749 | 0.9 | ||||
| Boy | 301 (50%) | 76 (49%) | 295 (49%) | 69 (48%) | ||||
| Girl | 299 (50%) | 80 (51%) | 310 (51%) | 75 (52%) | ||||
| Maternal characteristics | ||||||||
| Maternal prenatal alcohol use | 756 | 44 (7.3%) | 47 (30%) | <0.001 | 749 | 40 (6.6%) | 42 (29%) | <0.001 |
| Maternal prenatal any drug use | 756 | 10 (1.7%) | 26 (17%) | <0.001 | 749 | 9 (1.5%) | 28 (19%) | <0.001 |
| Maternal income to poverty threshold (at baseline) | 756 | 2.40 (2.57) | 1.52 (1.56) | <0.001 | 749 | 2.41 (2.58) | 1.48 (1.57) | <0.001 |
| Postnatal maternal smoking at ages 1 or 5 | 756 | <0.001 | 749 | <0.001 | ||||
| No maternal smoking at age 1 and 5 | 449 (75%) | 7 (4.5%) | 450 (74%) | 7 (4.9%) | ||||
| Maternal smoking at age 1 or age 5 | 151 (25%) | 149 (96%) | 155 (26%) | 137 (95%) | ||||
| Postnatal primary caregiver smoking in past month prior to visit | 756 | <0.001 | 749 | <0.001 | ||||
| No smoking | 478 (80%) | 23 (15%) | 513 (85%) | 45 (31%) | ||||
| Less than pack a day | 95 (16%) | 86 (55%) | 80 (13%) | 77 (53%) | ||||
| Pack or more a day | 27 (4.5%) | 47 (30%) | 12 (2.0%) | 22 (15%) | ||||
|
1
Mean (SD); n (%)
2
Welch Two Sample t-test; Pearson's Chi-squared test
|
||||||||
| Characteristic | Age 9 | Age 15 | ||||||
|---|---|---|---|---|---|---|---|---|
| N | Not exposed, N = 6001 | Smoke exposed, N = 1561 | p-value2 | N | Not exposed, N = 6051 | Smoke exposed, N = 1441 | p-value2 | |
| Percent global DNA methylation | 756 | 47.51 (0.74) | 47.59 (0.78) | 0.2 | 749 | 47.48 (0.85) | 47.58 (0.83) | 0.2 |
| Island methylation | 756 | 18.96 (0.61) | 19.07 (0.59) | 0.051 | 749 | 19.05 (0.61) | 19.14 (0.56) | 0.093 |
| Open Sea methylation | 756 | 70.36 (1.05) | 70.42 (1.10) | 0.5 | 749 | 70.22 (1.23) | 70.34 (1.22) | 0.3 |
| Shelf methylation | 756 | 75.33 (1.04) | 75.35 (1.10) | 0.8 | 749 | 75.19 (1.23) | 75.29 (1.21) | 0.4 |
| Shore methylation | 756 | 44.06 (0.82) | 44.17 (0.86) | 0.15 | 749 | 44.03 (0.94) | 44.15 (0.90) | 0.2 |
| Pediatric epigenetic clock (years) | 756 | 9.00 (0.85) | 9.01 (1.22) | 0.9 | 749 | 11.63 (1.77) | 11.64 (1.80) | >0.9 |
| GRIM epigenetic clock (years) | 756 | 24.7 (3.5) | 24.5 (3.3) | 0.6 | 749 | 30.5 (4.0) | 30.3 (4.2) | 0.6 |
| GRIM pack/yrs component | 756 | -5.6 (4.8) | -4.7 (5.0) | 0.041 | 749 | -4.0 (5.3) | -3.6 (5.1) | 0.4 |
| Epithelial cell proportion (saliva) | 756 | 0.04 (0.10) | 0.04 (0.08) | 0.3 | 749 | 0.08 (0.15) | 0.07 (0.14) | >0.9 |
| Immune cell proportion (saliva) | 756 | 0.96 (0.10) | 0.96 (0.08) | 0.3 | 749 | 0.92 (0.15) | 0.93 (0.14) | >0.9 |
| Polymethylation score for smoke exposure | 756 | -0.04 (0.22) | 0.09 (0.23) | <0.001 | 749 | -0.01 (0.22) | 0.11 (0.23) | <0.001 |
| Polymethylation score: coefficients for sustained smoking from newborn cordblood meta-analysis (mean-centered) | 756 | -0.06 (0.29) | 0.05 (0.27) | <0.001 | 749 | 0.01 (0.31) | 0.12 (0.31) | <0.001 |
| Polymethylation score: coeffcients for sustained smoking from older children peripheral blood meta-analysis (mean-centered) | 756 | -0.02 (0.23) | 0.09 (0.25) | <0.001 | 749 | -0.02 (0.27) | 0.07 (0.28) | <0.001 |
| Polymethylation score: coefficients for any smoking from newborn cordblood meta-analysis (mean-centered) | 756 | -0.04 (0.21) | 0.04 (0.19) | <0.001 | 749 | 0.01 (0.22) | 0.09 (0.22) | <0.001 |
| AHRR gene: percent cg05575921 methylation | 756 | 77.8 (5.2) | 76.8 (5.6) | 0.039 | 749 | 77 (6) | 76 (6) | 0.2 |
| MYO1G: cg04180046 | 756 | 35 (7) | 39 (8) | <0.001 | 749 | 35 (8) | 38 (8) | <0.001 |
| CYP1A1: cg05549655 | 756 | 18.7 (5.1) | 20.9 (5.5) | <0.001 | 749 | 18.3 (5.2) | 20.5 (5.1) | <0.001 |
| GFI1: cg14179389 | 756 | 5.70 (2.86) | 4.88 (2.62) | <0.001 | 749 | 5.74 (2.86) | 4.73 (1.78) | <0.001 |
| MYO1G: cg22132788 | 756 | 69 (10) | 73 (9) | <0.001 | 749 | 67 (11) | 70 (12) | 0.006 |
|
1
Mean (SD)
2
Welch Two Sample t-test
|
||||||||
## png
## 2
| Characteristic | Global methylation | Pediatric clock | Sustained smoking polymethylation score (newborns, cell-type controlled) | AHRR: cg05575921 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | |
| African ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 905 | 0.01 | 0.01, 0.02 | <0.001 | 905 | -0.17 | -0.36, 0.02 | 0.084 | 905 | 0.40 | 0.30, 0.50 | <0.001 | 905 | -1.1 | -1.6, -0.59 | <0.001 |
| European ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 234 | 0.01 | 0.01, 0.02 | <0.001 | 234 | 0.03 | -0.19, 0.24 | 0.8 | 234 | 0.60 | 0.38, 0.81 | <0.001 | 234 | -1.1 | -1.9, -0.36 | 0.004 |
| Hispanic ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 362 | 0.00 | -0.01, 0.01 | 0.4 | 362 | -0.05 | -0.38, 0.27 | 0.7 | 362 | 0.36 | 0.16, 0.55 | <0.001 | 362 | -0.56 | -1.5, 0.37 | 0.2 |
| Unstratified | ||||||||||||||||
| Prenatal maternal smoke exposed | 1501 | 0.01 | 0.01, 0.02 | <0.001 | 1501 | -0.14 | -0.27, 0.00 | 0.056 | 1501 | 0.42 | 0.33, 0.50 | <0.001 | 1501 | -0.95 | -1.3, -0.58 | <0.001 |
|
1
CI = Confidence Interval
|
||||||||||||||||
| Characteristic | Global methylation | Pediatric clock | Sustained smoking polymethylation score (newborns, cell-type controlled) | AHRR: cg05575921 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | |
| Age 9 models | ||||||||||||||||
| Prenatal maternal smoke exposed | 756 | 0.02 | -0.08, 0.12 | 0.7 | 756 | 0.00 | -0.15, 0.14 | >0.9 | 756 | 0.52 | 0.36, 0.67 | <0.001 | 756 | -1.1 | -1.7, -0.41 | 0.001 |
| Age 15 models | ||||||||||||||||
| Prenatal maternal smoke exposed | 749 | 0.08 | -0.03, 0.19 | 0.14 | 749 | 0.00 | -0.22, 0.21 | >0.9 | 749 | 0.46 | 0.30, 0.62 | <0.001 | 749 | -0.84 | -1.6, -0.06 | 0.034 |
| Longitudinal models | ||||||||||||||||
| Prenatal maternal smoke exposed | 1505 | 0.05 | -0.03, 0.14 | 0.2 | 1505 | 0.02 | -0.12, 0.17 | 0.8 | 1505 | 0.48 | 0.34, 0.63 | <0.001 | 1505 | -1.0 | -1.5, -0.39 | 0.001 |
|
1
CI = Confidence Interval
|
||||||||||||||||
| Characteristic | Global methylation | Pediatric clock | Sustained smoking polymethylation score (newborns, cell-type controlled) | AHRR: cg05575921 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | N | Beta | 95% CI1 | p-value | |
| African ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 907 | 0.05 | -0.06, 0.16 | 0.4 | 907 | 0.13 | -0.06, 0.32 | 0.2 | 907 | 0.52 | 0.34, 0.71 | <0.001 | 907 | -1.3 | -2.0, -0.55 | <0.001 |
| European ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 236 | -0.04 | -0.24, 0.16 | 0.7 | 236 | 0.00 | -0.24, 0.24 | >0.9 | 236 | 0.41 | 0.05, 0.77 | 0.027 | 236 | -1.2 | -2.4, 0.00 | 0.051 |
| Hispanic ancestry | ||||||||||||||||
| Prenatal maternal smoke exposed | 362 | 0.11 | -0.10, 0.31 | 0.3 | 362 | -0.33 | -0.72, 0.06 | 0.10 | 362 | 0.25 | -0.07, 0.58 | 0.13 | 362 | 0.37 | -1.0, 1.8 | 0.6 |
| Unstratified | ||||||||||||||||
| Prenatal maternal smoke exposed | 1505 | 0.05 | -0.03, 0.14 | 0.2 | 1505 | 0.02 | -0.12, 0.17 | 0.8 | 1505 | 0.48 | 0.34, 0.63 | <0.001 | 1505 | -1.0 | -1.5, -0.39 | 0.001 |
|
1
CI = Confidence Interval
|
||||||||||||||||
n n_total children in the Fragile Families and Child Wellbeing study. Base model: Child sex, maternal income to poverty ratio, immune cell proportion, plate, 1st two principal components from PCA on child genetic data, child age. Prenatal exposures model: base model + yes/no any prenatal maternal alcohol use, yes/no any prenatal other drug use. Secondhand smoking models: prenatal exposures model + yes/no any postnatal maternal/primary care giver smoking at age 1 or 5, pk/day in month prior to primary caregiver/maternal interview at age 9 or 15. Surrogate variable: including all surrogate variables| Age | Model | AUC | P value vs base model | P value vs base model + polymethylation score |
|---|---|---|---|---|
| Age 9 | Global methylation | 0.54 | 0.0000 | 0.0000 |
| Age 9 | Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.67 | 0.0560 | 0.0000 |
| Age 9 | AHRR: cg05575921 | 0.55 | 0.0000 | 0.0000 |
| Age 9 | Base model+No methylation | 0.73 | 1.0000 | 0.0003 |
| Age 9 | Base model+Global methylation | 0.73 | 0.5607 | 0.0003 |
| Age 9 | Base model+Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.77 | 0.0003 | 1.0000 |
| Age 9 | Base model+AHRR: cg05575921 | 0.74 | 0.1328 | 0.0334 |
| Age 15 | Global methylation | 0.53 | 0.0000 | 0.0000 |
| Age 15 | Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.65 | 0.0271 | 0.0000 |
| Age 15 | AHRR: cg05575921 | 0.54 | 0.0000 | 0.0000 |
| Age 15 | Base model+No methylation | 0.72 | 1.0000 | 0.0009 |
| Age 15 | Base model+Global methylation | 0.72 | 0.3802 | 0.0010 |
| Age 15 | Base model+Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.77 | 0.0009 | 1.0000 |
| Age 15 | Base model+AHRR: cg05575921 | 0.73 | 0.4054 | 0.0071 |
| Age | Model | AUC | P value vs base model | P value vs base model + polymethylation score with cell-type control |
|---|---|---|---|---|
| Age 9 | Any smoking polymethylation score (newborns) | 0.6215 | 0.0012 | 0.0000 |
| Age 9 | Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.6658 | 0.0560 | 0.0000 |
| Age 9 | Sustained smoking polymethylation score (newborns) | 0.6196 | 0.0010 | 0.0000 |
| Age 9 | Sustained smoking polymethylation score (older children) | 0.6341 | 0.0040 | 0.0000 |
| Age 9 | Base model+No methylation | 0.7252 | 1.0000 | 0.0003 |
| Age 9 | Base model+Any smoking polymethylation score (newborns) | 0.7598 | 0.0027 | 0.0142 |
| Age 9 | Base model+Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.7737 | 0.0003 | 1.0000 |
| Age 9 | Base model+Sustained smoking polymethylation score (newborns) | 0.7596 | 0.0027 | 0.0125 |
| Age 9 | Base model+Sustained smoking polymethylation score (older children) | 0.7666 | 0.0007 | 0.4181 |
| Age 15 | Any smoking polymethylation score (newborns) | 0.6062 | 0.0007 | 0.0000 |
| Age 15 | Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.6473 | 0.0271 | 0.0000 |
| Age 15 | Sustained smoking polymethylation score (newborns) | 0.6056 | 0.0006 | 0.0000 |
| Age 15 | Sustained smoking polymethylation score (older children) | 0.5923 | 0.0002 | 0.0000 |
| Age 15 | Base model+No methylation | 0.7213 | 1.0000 | 0.0009 |
| Age 15 | Base model+Any smoking polymethylation score (newborns) | 0.7566 | 0.0011 | 0.1124 |
| Age 15 | Base model+Sustained smoking polymethylation score (newborns, cell-type controlled) | 0.7664 | 0.0009 | 1.0000 |
| Age 15 | Base model+Sustained smoking polymethylation score (newborns) | 0.7569 | 0.0011 | 0.1270 |
| Age 15 | Base model+Sustained smoking polymethylation score (older children) | 0.7530 | 0.0075 | 0.1071 |